The purpose of the Mouse Core will be to provide a centralized service-oriented facility to insure the capacity of each participating project lab to produce and maintain transgenic and gene-disrupted mice. The Mouse Core will also serve the projects of this Program by supporting the infrastructure of two lung injury models that will be extensively utilized by the projects, namely exposure to cigarette smoke and Sendai virus infection, overseeing the use of standardized protocols of each model and ensuring regulatory compliance through one centralized facility. Support of the Sendai infection model by the Mouse Core would also be provided for use in in vitro cell culture models generated within the morphology core (air liquid interface cultures of tracheal epithelial cells, and Clara cell/alveolar epithelial cell cultures). Furthermore, in association with these models, the Mouse Core will support individual projects by measuring pulmonary physiological parameters such as resistance and compliance in vivo using the BUXCO system. Thus, the Mouse Core will be an important part of this Program Project Grant. The major components of the Mouse Core, including the transgenic/knockout production unit, the smoking facility, and the Sendai infection model are each supported by dedicated space within our animal facility and are fully equipped. While the Mouse Core was part of this Program Project Grant during the previous funding cycle, this core was initially developed in our Pulmonary Division in 1995 and has been extensively utilized by Project Investigators and Core Directors on this application for many years. It is staffed by personnel with a collective extenisive track record of expertise and productivity in this area. The Mouse Core has been responsible for generating over 100 transgenic and knockout lines, with multiple founders/chimeras of each. Many of the mice which have been and will be made by this core will further serve to facilitate collaborative interactions amongst Project Investigators. As this Program would jointly support the transgenic/knockout production unit with two other NIH center grants, this will allow us to realize an economy of scales and lower production costs per mouse generated.